Inadequate healing is also common. Scar formation starts with transcription of pro-collagen, which undergoes post-translational hydroxylation of the abundant proline and lysine residues. This promotes the cross-linking within and between collagen strands that provides tensile strength which begins the healing process. The prolyl and lysyl hydroxylases that catalyze this reaction depend on the substrate oxygen. The Km (substrate concentration at which the velocity of the reaction is half-maximal) for O2 of prolyl hydroxylase has been variously estimated at 20, 25, and 100 mmHg. Even using the most conservative estimate, these data suggest that proline hydroxylation of collagen (e.g., scar formation) will be PO2 dependent through the range of 0 to ≈200 mmHg, with 90% of the effect occurring by 90 mmHg. In vitro and in vivo animal evidence supports this theory. Inadequate healing is associated with anastomotic leakage, wound dehiscence, and bleeding.